Evaluating narrow windows of maternal exposure to ozone and preterm birth in a large urban area in Southeast Texas.

The association between O3 exposure and preterm birth (PTB) remains unclear. We evaluated associations for three categories of PTB and O3 in Harris County, Texas, during narrow periods of gestation. We computed two sets of exposure metrics during every 4 weeks of pregnancy for 152,214 mothers who delivered singleton, live-born infants in 2005-2007, accounting first for temporal variability and then for temporal and spatial sources of variability in ambient O3 levels. Associations were assessed using multiple logistic regression. We also examined the potential for a fixed cohort bias. In the bias-corrected cohort where associations were somewhat stronger, elevated odds ratios (ORs) per 10 parts per billion increase in O3 exposure (county-level metric) were detected for the fifth (OR=1.08, 95% confidence interval (CI): 1.04-1.12), sixth (OR=1.05, 95% CI=1.01-1.09), and seventh (OR=1.07, 95% CI=1.03-1.10) 4-week periods of pregnancy for late PTB (33-36 completed weeks gestation), the fifth (OR=1.13, 95% CI=1.02-1.25) and seventh (OR=1.15, 95% CI=1.04-1.27) 4-week periods of pregnancy for moderate PTB (29-32 completed weeks gestation), and the fifth (OR=1.21, 95% CI=1.08-1.36) 4-week period of pregnancy for severe PTB (20-28 completed weeks gestation). Conversely, decreased odds were found in the first 4-week period of pregnancy for severe PTB (OR=0.83, 95% CI=0.74-0.94). Associations were slightly attenuated using the spatially interpolated (kriged) metrics, and for women who did not work outside of the home. Our analyses confirm reports in other parts of the United States and elsewhere with findings that suggest that maternal exposure to ambient levels of O3 is associated with PTB.

Prioritizing environmental issues around the world: opinions from an international Central and Eastern European environmental health conference.

BACKGROUND: As the next generation of scientists enters the field of environmental health, it is imperative that they view their contributions in the context of global environmental stewardship. In this commentary, a group of international graduate students facilitated by three experienced environmental health scientists present their views on what they consider to be the global environmental health concerns of today. This group convened initially in October 2004 at an international health conference in Prague, Czech Republic. OBJECTIVES: In this report we identify perceived environmental health concerns that exist around the world, with a focus on Central and Eastern Europe. Additionally, we address these perceived problems and offers some potential solutions. DISCUSSION: At the meeting, students were invited to participate in two panel discussions. One group of young international scientists identified several significant global environmental health concerns, including air pollution, occupational hazards, and risk factors that may exacerbate current environmental health issues. The second panel determined that communication, education, and regulation were the mechanisms for addressing current environmental challenges. CONCLUSIONS: In this commentary we expand on the views presented at the meeting and represent the concerns of young investigators from nine different countries. We provide ideas about and support the exchange of information between developed and developing countries on how to handle the environmental health challenges that face the world today.

Thyroid-hormone-disrupting chemicals: evidence for dose-dependent additivity or synergism.

Endocrine disruption from environmental contaminants has been linked to a broad spectrum of adverse outcomes. One concern about endocrine-disrupting xenobiotics is the potential for additive or synergistic (i.e., greater-than-additive) effects of mixtures. A short-term dosing model to examine the effects of environmental mixtures on thyroid homeostasis has been developed. Prototypic thyroid-disrupting chemicals (TDCs) such as dioxins, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers have been shown to alter thyroid hormone homeostasis in this model primarily by up-regulating hepatic catabolism of thyroid hormones via at least two mechanisms. Our present effort tested the hypothesis that a mixture of TDCs will affect serum total thyroxine (T4) concentrations in a dose-additive manner. Young female Long-Evans rats were dosed via gavage with 18 different polyhalogenated aromatic hydrocarbons [2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin-like PCBs] for 4 consecutive days. Serum total T4 was measured via radioimmunoassay in samples collected 24 hr after the last dose. Extensive dose-response functions (based on seven to nine doses per chemical) were determined for individual chemicals. A mixture was custom synthesized with the ratio of chemicals based on environmental concentrations. Serial dilutions of this mixture ranged from approximately background levels to 100-fold greater than background human daily intakes. Six serial dilutions of the mixture were tested in the same 4-day assay. Doses of individual chemicals that were associated with a 30% TH decrease from control (ED30), as well as predicted mixture outcomes were calculated using a flexible single-chemical-required method applicable to chemicals with differing dose thresholds and maximum-effect asymptotes. The single-chemical data were modeled without and with the mixture data to determine, respectively, the expected mixture response (the additivity model) and the experimentally observed mixture response (the empirical model). A likelihood-ratio test revealed statistically significant departure from dose additivity. There was no deviation from additivity at the lowest doses of the mixture, but there was a greater-than-additive effect at the three highest mixtures doses. At high doses the additivity model underpredicted the empirical effects by 2- to 3-fold. These are the first results to suggest dose-dependent additivity and synergism in TDCs that may act via different mechanisms in a complex mixture. The results imply that cumulative risk approaches be considered when assessing the risk of exposure to chemical mixtures that contain TDCs.

Comparative responsiveness of hypothyroxinemia and hepatic enzyme induction in Long-Evans rats versus C57BL/6J mice exposed to TCDD-like and phenobarbital-like polychlorinated biphenyl congeners.

Numerous mechanisms have been postulated to explain how polyhalogenated aromatic hydrocarbons alter thyroid homeostasis with almost all data derived from studies using the rat. This study compared the sensitivity of rats and mice to polychlorinated biphenyl (PCB)-induced hypothyroxemia. Male and female C57BL/6J mice and Long-Evans rats were dosed orally for 4 consecutive days with either PCB126 (0.03-300.0 microg/kg/day) or PCB153 (0.3-300.0 mg/kg/day). Trunk blood and livers were collected 24 h after the last dose and used to determine total serum thyroxine (T(4)) and hepatic microsomal T(4) glucuronidation activity. Hepatic microsomal ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-deethylase (PROD) activities were also determined as markers for Ah receptor or phenobarbital response unit activation, respectively. PCB126 did not affect T(4) in the mouse but decreased T(4) (up to 50%) in the rat. PCB153 decreased T(4) (up to 80%) in both the rat and the mouse. PCB126 increased EROD in both rats (12- to 22-fold) and mice (15- to 20-fold). PCB153 induced hepatic PROD activity in both rats (30-fold) and mice (4-fold). T(4) glucuronidation was increased approximately 2- to 3-fold in both rats and mice treated with PCB153. PCB126 increased T(4) glucuronidation 13-fold in rats but only marginally (20%) in mice at the highest doses. Western blot analysis confirmed the PCB126-induced changes in expression of UGT1A in rats and the minimal increase in mice. These data suggest that species differences in response to chemicals that induce hypothyroxinemia are due to differential induction of hepatic UGT enzymes.